Lirioresinol B dimethyl ether inhibits NF-κB and COX-2 and activates IκBα expression in CCl4-induced hepatic fibrosis

BMC Complement Med Ther. 2020 Feb 11;20(1):49. doi: 10.1186/s12906-020-2839-3.

Abstract

Background: Inflammation is one of the key components in the initiation and progression of hepatic diseases. If not treated, inflammation may cause cell dysplasia, and ultimately cancer. In the current study, we investigated the anti-inflammatory and anti-cancer activities of plant isolated compound Lirioresinol B Dimethyl Ether (LBDE) extracted from the seeds of Magnolia fargesii CHENG (Magnoliaceae) against HepG2 cells as well as in BALB/C male mice.

Methods: We assessed the antioxidant and anti-proliferative effects of plant compounds using DPPH assay and HepG2 cell lines. Carbon tetrachloride (CCl4) and Diethylnitrosamine (DEN) were used to induce liver cell dysplasia followed by hepatocellular carcinoma (HCC) in BALB/C male mice for 12 weeks. We investigated the underlying mechanism by using histopathology and immunoblot experiments.

Results: Intraperitoneal injection of LBDE (50 mg/kg body weight/day) inhibited CCl4-induced HCC. Free radical scavenging assay shows the strong anti-oxidant activity of LBDE. Western blot results show that LBDE down-regulated nuclear factor kappa B (NFκB) and cyclooxygenase (COX-2) by preventing the phosphorylation of I kappa B alpha (IκBα) in CCl4 treated group. LBDE also improved liver function by decreasing Alkaline Phosphatase (ALP), aspartate aminotransferase (AST) and Alanine Aminotransferase (ALT) levels. Histopathology results revealed that LBDE decreased granulomas and express normal morphology of hepatocytes.

Conclusions: These preliminary results show that LBDE has the potential to inhibit CCl4-induced liver cell dysplasia and prevents cancer development by regulating NFκB/COX-2 activation.

Keywords: Antioxidant; COX-2; Hepatic fibrosis; Inflammation; Lirioresinol B dimethyl ether; NFκB.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antineoplastic Agents / pharmacology
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Disease Models, Animal
  • Furans / pharmacology*
  • Hep G2 Cells
  • Humans
  • Liver Cirrhosis / drug therapy*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Molecular Structure
  • NF-KappaB Inhibitor alpha / metabolism*
  • NF-kappa B / antagonists & inhibitors*
  • Plant Extracts / pharmacology*
  • Seeds

Substances

  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • Cyclooxygenase 2 Inhibitors
  • Furans
  • NF-kappa B
  • Plant Extracts
  • lirioresinol B dimethyl ether
  • NF-KappaB Inhibitor alpha
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2